Analytical procedures were developed for the estimation of total body turnover of norepinephrine (NE) and dopamine (DA) in both humans and experimental animals. These procedures were employed to evaluate total body NE and DA in schizophrenic and depressed patients on and off medication. To determine the relationship between total body turnover of catecholamines and brain amine turnover and metabolism, supplementary experiments were carried out on rats exposed to the same treatments as those administered to humans. The results of our findings are as follows: 1. Total body NE turnover (sum NE) is elevated in major depression with melancholia but not in depression without melancholia. 2. Five forms of antidepression treatments (low doses of clorgyline, desipramine (DMI), zimelidine (ZMI), electroconvulsive treatment (ECT) and lithium) significantly reduced sum NE. Sum DA was not consistently reduced. 3. There is a tendency for sum DA but not sum NE to be reduced in chronic schizophrenia. When sum DA and sum NE were evaluated, chronic schizophrenic patients had significantly lower ratios than sex and age matched controls. Haloperidol treatment normalized these ratios. 4. Consistent with human analyses, DMI, ZMI and lithium chronic treatments significantly reduced sum NE in rats as well as in the hypothalamus, suggesting a positive correlation between total body turnover of NE and brain NE turnover. ECT significantly increased sum NE and brain NE turnover. These four types of antidepressants produced inconsistent changes in sum DA and caudate nucleus turnover of DA. DMI and ZMI, significantly reduced caudate nucleus DA turnover suggesting some role of brain DA in the therapeutic actions of these two drugs. 5. As part of our exploratory studies we have also evaluated the in vivo effects of 3 classes of monoamine oxidase inhibitors (MAOI) on central and peripheral catecholamines. Our results indicated a good correlation between changes in sum NE and sum DA and those occurring in the brain. The three MAOIs employed were pargyline, clorgyline and deprenyl.